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81.
Visceral leishmaniasis (VL) or kala-azar continues to persist as one of the major public health problems in many tropical countries. However, no effective treatment for radical cure of the disease is yet available. Miltefosine, an alkyl phospholipid compound, is the first orally effective drug, which has shown 98% cure rate of VL patients during phase III clinical trial in India. Since this drug requires long course of treatment and has long half-life, there are fairly good chances of emergence of resistance. Furthermore, this drug has produced severe side-effects in some of the cases.We therefore examined the possibility of minimizing these effects by applying miltefosine in lower doses in combination with picrloviv, an immunomodulator against Leishmania donovani in hamsters (Mesocricetus auratus). The picroliv per se showed no antileishmanaial potential. However, when given with suboptimal dose of miltefosine, it enhanced efficacy of the latter from 45 to 86% on day 7 post treatment and from 32 to 64% on day 28 post treatment. Interestingly, the efficacy of this combination was as good as the curative dose of miltefosine alone. Thus, this combination appears to offer a fruitful strategy for treatment of VL.  相似文献   
82.
AIMS: The main purpose of this study was to evaluate the regional diastolic function in Chagas' disease using tissue Doppler imaging (TDI). METHODS AND RESULTS: Seventy-seven patients were evaluated and divided into three groups: group 0, control; group 1, chagasic patients with normal ECG; and group 2, chagasic patients with abnormal ECG. The following parameters were evaluated: E and A waves, E/A ratio, deceleration time and the isovolumic relaxation time by pulsed wave Doppler and analysis of early (e') and late (a') filling waves by means of TDI, in basal segment of the septal, anterior, inferior, posterior and lateral walls of the left ventricle. The only index of the transmitral flow that presented a significant difference between the chagasic patients and the controls was the deceleration time. As regards the TDI, a significant difference occurred between the various groups in relation to the e' wave, especially in the septal, inferior and posterior walls of the left ventricle. CONCLUSION: TDI proved itself a more sensitive technique for the study of the diastolic function in Chagas' disease than conventional Doppler echocardiography, bringing to light regional abnormalities and allowing differentiation between normal and chagasic individuals with or without cardiomyopathy. TDI could be potentially useful in clinical work and in the stratification of risk of these patients.  相似文献   
83.
OBJECTIVE:. To assess the efficacy and safety of etanercept in a large cohort of children with refractory systemic onset juvenile rheumatoid arthritis (SOJRA). METHODS: Standardized questionnaires were sent to US pediatric rheumatologists about patients with SOJRA treated with etanercept. Data were collected at baseline and at the last visit on etanercept. Response to treatment was assessed and compared to baseline as the mean percentage reduction in the following: acute phase reactants, prednisone dose, active joint count, and physician global assessment of disease activity. Response was defined as poor if the mean reduction was < 30%, fair if 30% to < 50%, good if 50% to < 70%, and excellent if > 70%. RESULTS: We analyzed data obtained by survey of 82 SOJRA patients treated with etanercept for a mean of 25 months. Poor response to treatment was observed in 45% of the children, fair response in 9%, good in 13%, and excellent in 33%. Baseline steroid therapy could be discontinued in 27/59 (46%) patients. One or more disease flares occurred in 45% of all patients. Twenty-nine patients (35%) discontinued therapy, mostly due to lack of response or flare. There were 32 adverse event reports, most not considered serious, except for 2 cases of macrophage activation syndrome. CONCLUSION: In this cohort of children with SOJRA, 46% had a good or excellent response, and most were able to reduce concomitant corticosteroid doses. The response to etanercept was fair or poor in more than half our study population, and disease flares were common. Due to the unique cytokine profile of SOJRA, tumor necrosis factor blockade may not be the optimal therapeutic approach for children with treatment-resistant SOJRA.  相似文献   
84.
Predictive factors for response to lamivudine in chronic hepatitis B   总被引:12,自引:0,他引:12  
BACKGROUND: Lamivudine has been shown to be an efficient drug for chronic hepatitis B (CHB) treatment. AIM: To investigate predictive factors of response, using a quantitative method with high sensitivity. METHODS: We carried out a prospective trial of lamivudine in 35 patients with CHB and evidence for viral replication, regardless to their HBeAg status. Lamivudine was given for 12 months at 300 mg daily and 150 mg thereafter. Response was considered when DNA was undetectable by PCR after 6 months of treatment. Viral replication was monitored by end-point dilution PCR. Mutation associated with resistance to lamivudine was detected by DNA sequencing in non-responder patients. RESULTS: Response was observed in 23/35 patients (65.7%) but only in 5/15 (33.3%) HBeAg positive patients. Only three pre-treatment variables were associated to low response: HBeAg (p = 0.006), high viral load (DNA-VHB > 3 x 10(6) copies/ml) (p = 0.004) and liver HBcAg (p = 0. 0028). YMDD mutations were detected in 7/11 non-responder patients. CONCLUSIONS: HBeAg positive patients with high viral load show a high risk for developing drug resistance. On the other hand, HBeAg negative patients show a good response to lamivudine even with high viremia.  相似文献   
85.
PURPOSE: The aim of this preliminary study was to present an alternative method to assess the anal sphincters by ultrasonography using a conventional ultrasound surface probe by transperineal approach. METHODS: Transperineal ultrasonography was performed in 20 asymptomatic volunteers to assess the anal sphincters. Ultrasonographic findings were compared with conventional anal endosonography pictures available in the literature. RESULTS: Images of the anal sphincters obtained by transperineal ultrasound were found to be similar to those produced by conventional anal endosonography. Internal and external anal sphincters were easily demonstrated in addition to mucosal and submucosal layers. CONCLUSIONS: Transperineal ultrasonography is a new technique that enables imaging of anal sphincters and anal canal structures with potential application in functional and inflammatory anorectal disorders.Dr. Kleinübing was supported by grant from National Agency CAPES Brazil.Presented at 1° Encontro Catarinense de Colo-Proctologia, Joinville—SC—Brazil, December 12, 1997.  相似文献   
86.
We present four FIPA kindred discussing clinical and molecular data and emphasizing the differences regarding AIP status, as well as the importance of genetic screening. Family 1 consists of five patients harboring somatotropinomas with germline E24X mutation in AIP. In one of the patients, acromegaly was diagnosed through active screening, being cured by surgery. Families 2 and 3 are composed of two patients with non-functioning pituitary adenomas. Family 4 comprises patients harboring a prolactinoma and a somatotropinoma. No mutations in AIP were found in these families. No patient in Family 1 was controlled with octreotide treatment, while the acromegalic patient in Family 4 was controlled with octreotide LAR. In conclusion, FIPA is a heterogeneous condition, which may be associated with AIP mutation. Genomic and clinical screening is recommended in families with two or more members harboring pituitary adenomas, allowing early diagnosis and better outcome.  相似文献   
87.
The cell wall of Staphylococcus aureus is characterized by an extremely high degree of cross-linking within its peptidoglycan (PGN). Penicillin-binding protein 4 (PBP4) is required for the synthesis of this highly cross-linked peptidoglycan. We found that wall teichoic acids, glycopolymers attached to the peptidoglycan and important for virulence in Gram-positive bacteria, act as temporal and spatial regulators of PGN metabolism, controlling the level of cross-linking by regulating PBP4 localization. PBP4 normally localizes at the division septum, but in the absence of wall teichoic acids synthesis, it becomes dispersed throughout the entire cell membrane and is unable to function normally. As a consequence, the peptidoglycan of TagO null mutants, impaired in wall teichoic acid biosynthesis, has a decreased degree of cross-linking, which renders it more susceptible to the action of lysozyme, an enzyme produced by different host organisms as an initial defense against bacterial infection.  相似文献   
88.
Idiopathic varices of the entire colon are very rare. We report on a 64-year-old patient with massive lower gastrointestinal hemorrhage from an extensive ileocolonic varix. Diagnosis was established by colonoscopy. The patient underwent an emergency ileocolectomy with satisfactory results. This rare case shows the importance of colonoscopy in the evaluation of patients with lower gastrointestinal hemorrhage and reminds us that sometimes the diagnosis is not what we expect. Recognition of this abnormality is important because varices may be the cause of massive lower gastrointestinal hemorrhage.  相似文献   
89.
BACKGROUND: Peak oxygen consumption and resting left ventricular ejection fraction (LVEF) are independent predictors of survival in adult heart failure (HF) patients. Aim: To evaluate these factors in children. METHODS: We prospectively studied 31 children with NYHA class I to III HF (mean LVEF 26+/-10%; mean age 8.6+/-1.9 years). All had dilated cardiomyopathy and were awaiting heart transplantation. A cardiopulmonary treadmill exercise test was performed and LVEF determined by radionuclide ventriculography. RESULTS: During a median follow-up of 1282 days, 20 children reached at least one end-point (death or heart transplantation). Clinical data from the 11 children without events and the 20 children with events are as follows: NYHA class 1+/-0 vs. 2+/-0.9 (p<0.01); SBP 118+/-17 vs. 102+/-16 (p=0.01); DBP 70+/-10 vs. 61+/-10 (p=0.02); heart rate 165+/-22 vs. 148+/-22 (NS); double-product 19+/-4 vs. 15+/-4 (p=0.01); end-tidal carbon dioxide tension (PetCO2) 35+/-5 vs. 30+/-6 (NS); oxygen consumption (VO2) 22+/-5.4 vs. 18.3+/-5.7 (NS); exercise time 19+/-4 vs. 13+/-6 (p<0.003), and LVEF 31+/-8 vs. 22+/-10 (p=0.02). These variables all correlated with prognosis on univariate analysis. In multivariate analysis, only decreasing exercise time and LVEF were predictive of events during follow-up (p<0.001 and 0.04). CONCLUSION: These findings suggest that reduction in LVEF and exercise tolerance in children with heart failure is predictive of functional status.  相似文献   
90.
Effective treatment of gestational diabetes is important as an attempt to avoid unfavorable maternal and fetal outcomes. The objective of this paper is to describe the available therapies to optimize gestational diabetes treatment and to suggest a multidisciplinary approach algorithm. Nutrition therapy is the first option for the majority of these pregnancies; light to moderate physical activity is recommended in the absence of obstetrical contraindications. Medical treatment is recommended if glycemic control is not achieved or if excessive fetal growth is detected by ultrasound. Insulin is the standard treatment although oral antidiabetic drugs have recently been considered an effective and safe option. The monitoring of gestational diabetes treatment includes capillary glucose measurements and evaluation of fetal abdominal circumference by ultrasound performed around the 28th gestational week.  相似文献   
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